Among various processes of polymerization reactions, solution polymerization process is typically applied to synthesize biodegradable polymers, in which monomers, catalysts, and polymers are all dissolved in a solvent. The reaction begins with the monomers and the catalysts dissolved in a solvent in a reactor. With the activated catalysts the monomers are continuously added to the growing polymer chain at the catalyst active site by coordinate covalent bonding. The dissolution of the polymer in a solvent is maintained to perform the reaction in a single homogeneous liquid phase.
When the reaction is finished, the solution in a reactor becomes a mixture containing the polymer obtained by the synthesis, unreacted monomers, the solvent, and a small amount of catalyst. Accordingly, after the reaction, a process for selectively recovering the polymer from the solution is required.
The presence of monomers in the synthesis of polymers is frequently problematic. For example, in the synthesis of biodegradable polymers such as homopolymers or copolymers based on lactide (L-lactide, D-lactide, DL-lactide, meso-lactide), glycolide, epsilon-caprolactone, dioxanone, trimethylene carbonate, delta-valerolactone, gamma-butyrolactone the presence of monomers is undesirable for various reasons. In many instances monomers decompose more rapidly than biodegradable polymers on exposure to moisture. Consequently, the implantation of monomer-containing biodegradable polymers would therefore lead to a greatly accelerated breakdown of the material in the body. For the same reason, the stability in storage of monomer-containing polymers and implants or pharmaceutical formulations produced therefrom is markedly impaired.
It is well known that drug depots are prepared by well known thermoplastic processes such as melt extrusion or injection molding. The stability of biodegradable polymers is also impaired during thermoplastic processing if residual contents of monomers are present.
In other instances, the encapsulation behavior of non-purified biodegradable polymers is different from that of purified polymers, as are the release behavior and the breakdown behavior. Encapsulated active ingredients, such as peptides, can become damaged or destroyed as a result of the greater amount of free acid present in monomer contaminated polymers compared to purified polymers.
During the synthesis reactions, the residual monomer content of the crude polymer is often difficult to control. Variability in the residual monomer content then automatically also leads to intolerable batch-to-batch variations in the breakdown rate, the stability in storage and the processing stability, so materials of reproducible quality cannot be obtained without a subsequent purification step to reduce the amount of residual monomers.
It would therefore be desirable to develop improved polymer recovery and purification methods that minimize the presence of monomers in melt extrudable polymers and at the same time reduce the number of unit operations required to produce the same thereby reducing both the time and cost of manufacturing.